JP2018515531A5

JP2018515531A5 -

Info

Publication number: JP2018515531A5
Application number: JP2017559113A
Authority: JP
Filing date: 2016-05-13
Publication date: 2019-06-13
Anticipated expiration: 2036-05-13

Claims

A compound of formula (I), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof;
During the ceremony
Ring Het is heterocyclyl,
Each Y ₁ , Y ₂ and Y ₃ is CR _a or N respectively, where 0-2 of Y ₁ , Y ₂ and Y ₃ is N,
Each Z ₁ , Z ₂ , Z ₃ , Z ₄ and Z ₅ is CR _a or N respectively, where 0-3 of Z ₁ , Z ₂ , Z ₃ , Z ₄ and Z ₅ is N,
L _{is, * - NR b -C (O} ) - (CR b R c) n -, or _{* -C (O) -NR b -} (CR b R c) n - and is, where * marked groups Is linked to a ring comprising Y ₁ , Y ₂ and Y ₃ ,
Each _R _1, R 2, _{R 6} and _{R 7} are each hydrogen, halo, alkyl or haloalkyl,
At each occurrence , R ₃ is each hydrogen, halo, alkyl, alkylamino, alkoxy, haloalkyl, haloalkoxy, or cycloalkyl, or two R ₃ on the same carbon atom are both oxo (= O) groups Form
R ₄ is hydrogen, alkyl or alkoxy,
R ₅ is _alkyl, - _(CH ₂₎ a _n NR _{b R} c or hydroxyalkyl,
R _a is hydrogen, alkyl, alkoxy, halo, cycloalkyl or aryl
R _b and R _c are each independently hydrogen, alkyl or alkoxyalkyl, or R _b and R _c on the same atom together form a ring ,
m is 0 to 3 and
The compound wherein n is 0 to 3.

A compound of formula (IA);
Or a salt thereof or a stereoisomer pharmaceutically acceptable compound according to claim 1.

A compound of formula (IB);
Or a salt thereof or a stereoisomer pharmaceutically acceptable compound according to claim 1.

A compound of formula (IC);
Or a salt thereof or a stereoisomer pharmaceutically acceptable compound according to claim 1.

Compounds of the formula (ID);
Or a salt thereof or a stereoisomer pharmaceutically acceptable compound according to claim 1.

A compound of formula (IE);
Or the compound of Claim 1 which is a pharmaceutically acceptable salt or its stereoisomer.

A compound of formula (IF);
Or the compound of Claim 1 which is a pharmaceutically acceptable salt or its stereoisomer.

A compound of formula (IG);
Or the compound of Claim 1 which is a pharmaceutically acceptable salt or its stereoisomer.

The ring Het may be pyridyl, pyridazinyl, pyridazinone, pyrimidinyl, pyrazinyl, pyrazolyl, imidazopyrazinyl, imidazopyridinyl, pyrrolopyrazinyl, thienyl, benzodioxolyl, benzimidazolyl, imidazolyl, imidazopyridazinyl, or tetrahydroisoquinolinyl. The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

Is
The compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

L is, * - NHCOCH ₂ - or * -CONHCH ₂ - a, where at * marked groups are linked to the ring containing _Y 1, _{Y 2} and _{Y 3,} one of claims 1 to 8 1 Or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof.

9. A compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof or a salt thereof, wherein each R ₁ , R ₂ , R ₆ and R ₇ is hydrogen and R ₄ is alkyl. Stereoisomer.

R ₅ is alkyl, A compound according to any one of claims 1 to 8, or a pharmaceutically acceptable salt or a stereoisomer thereof.

12. The compound according to any one of the preceding claims, or a pharmaceutically acceptable salt thereof or a stereoisomer thereof, wherein R _a is hydrogen or alkyl.

The compound selected from the following, or a pharmaceutically acceptable salt thereof or a stereoisomer thereof:

The compound of the following formula (compound 104), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

The compound of the following formula (Compound 107), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

The compound of the following formula (Compound 110), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

The compound of the following formula (Compound 125), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

The compound of the following formula (Compound 129), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

A compound of the following formula (Compound 56), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

The compound of the following formula (compound 43), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

The compound of the following formula (Compound 47), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

A compound of the following formula (Compound 2), or a pharmaceutically acceptable salt thereof or a stereoisomer thereof.

26. A pharmaceutical composition comprising a compound of any one of claims 1-25, or a pharmaceutically acceptable salt thereof or a stereoisomer thereof, and at least one pharmaceutically acceptable carrier or excipient.

26. Use of a compound of any one of claims 1 to 25 in the manufacture of a medicament for the treatment of an immune or inflammatory disease.

26. Use of a compound according to any one of claims 1 to 25 in the manufacture of a medicament for use in the treatment of a disorder or disease mediated by RORγ, wherein the disorder or disease mediated by RORγ is an immune disease or inflammation Is a sexual disease, use.

Diseases or diseases include rheumatoid arthritis, psoriasis, chronic graft-versus-host disease, acute GVHD, Crohn's disease, inflammatory bowel disease, multiple sclerosis, systemic lupus erythematosus, celiac disease, idiopathic thrombocytopenic purpura 29. The use according to claim 27 or 28, wherein the patient is myasthenia gravis, Sjögren's syndrome, asthma, epidermal hyperplasia, scleroderma or ulcerative colitis.

Diseases or diseases include cartilage inflammation, bone deterioration, arthritis, juvenile arthritis, juvenile rheumatoid arthritis, small joint juvenile rheumatoid arthritis, articulated juvenile rheumatoid arthritis, systemic onset juvenile rheumatoid arthritis, juvenile anemia Spondylitis, juvenile enteritis arthritis, juvenile reactive arthritis, juvenile Reiter syndrome, SEA syndrome, juvenile dermatomyositis, juvenile psoriatic arthritis, juvenile scleroderma, juvenile systemic lupus erythematosus, juvenile blood vessels Inflammation, rheumatoid arthritis, arthritic rheumatoid arthritis, systemic rheumatoid arthritis, ankylosing spondylitis, enterocolitis, reactive arthritis, Reiter syndrome, dermatomyositis, psoriatic arthritis, vasculitis, myositis, multiple Myositis, osteoarthritis, polyarteritis nodosa, Wegener's granuloma, arteritis, polymyalgia rheumatica, sarcoidosis, sclerosis, primary cholangiosclerosis, hard Cholangitis, dermatitis, atopic dermatitis, atherosclerosis, Still's disease, chronic obstructive pulmonary disease, Guillain-Barre's disease, type 1 diabetes, Graves' disease, Addison's disease, Raynaud's phenomenon, autoimmune hepatitis, 28. The method according to claim 27, which is psoriatic epidermal hyperplasia, psoriasis vulgaris, psoriatic psoriasis, reverse psoriatic psoriasis, pustular psoriasis, psoriatic erythroderma, or an immune disease associated with or resulting from pathogenic lymphocyte activity. Or use according to 28.